Neutrophil gelatinase associated lipocalin (NGAL) is elevated in type 2 diabetics with carotid artery stenosis and reduced under metformin treatment

Cardiovascular Diabetology

Original Investigation

A. Kaider¹  W. J. Weninger²  S. Stojkovic³  J. Wojta⁴  S. Demyanets⁵  A. Piechota-Polanczyk⁶  N. Kozakowski⁷  W. Eilenberg⁸  I. Huk⁸  J. Nanobachvili⁸  C. Neumayer⁹ 

[1] Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria;Center of Anatomy and Cell Biology, Medical University of Vienna, Vienna, Austria;Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria;Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna, Vienna, Austria;Core Facilities, Medical University of Vienna, Vienna, Austria;Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria;Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Krakow, Poland;Department of Pathology, Medical University of Vienna, Vienna, Austria;Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria;Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria;Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Krakow, Krakow, Poland;

关键词: NGAL;    Lipocalin;    Atherosclerosis;    Carotid artery stenosis;    Inflammation;    Type II diabetes;    Metformin;   

DOI  :  10.1186/s12933-017-0579-6

 received in 2017-06-08, accepted in 2017-07-26,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundNeutrophil gelatinase-associated lipocalin (NGAL), an acute phase protein released by neutrophils, has been described as biomarker of inflammatory states. Type 2 diabetes mellitus (T2DM) is characterized by increased inflammation and an elevated risk for embolization of carotid artery stenosis (CAS). We aimed to explore the role of NGAL systemically and in plaques of diabetics undergoing carotid endarterectomy. Moreover, the potential anti-inflammatory effect of metformin on NGAL was addressed in diabetics.MethodsSerum NGAL and matrix metalloproteinase (MMP)-9/NGAL levels were measured in 136 patients (67 with T2DM vs. 69 non-diabetics) by specific ELISA. Endarterectomy samples were graded histologically according to the American Heart Association´s classification. NGAL mRNA expression was detected using RealTime-PCR in carotid endarterectomy specimens.ResultsSerum NGAL [median 107.4 ng/ml (quartiles: 75.2–145.0) vs. 64.4 (50.4 –81.3), p < 0.0001] and MMP-9/NGAL [41.5 ng/ml (20.8–63.9) vs. 27.6 (16.0–42.4), p = 0.017] were significantly elevated in diabetics compared to non-diabetics, as were leukocytes, neutrophils, C-reactive protein and fibrinogen (all p < 0.05). In patients with symptomatic and asymptomatic CAS diabetics had higher NGAL levels compared to non-diabetics [128.8 ng/ml (100.8–195.6) vs. 64.8 (48.9–82.2] and [101.6 ng/ml (70.1–125.3) vs. 63.8 (51.0–81.3), respectively, both p < 0.0001]. Presence of T2DM and type VI plaques (with surface defect, hemorrhage or thrombus) had a profound impact on NGAL levels (both p < 0.01) in multiple linear regression analysis. NGAL mRNA was detectable in 95% of analyzed carotid artery lesions of diabetics compared to 5% of non-diabetics (p < 0.0001). Accordingly, cerebral embolization was more frequent in diabetics (52.2% vs. 29%, p = 0.006). Metformin treatment was associated with decreased NGAL [60.7 ng/ml (51.9–69.2) vs. 121.7 (103.7–169.9), p < 0.0001] and MMP-9/NGAL [20.8 ng/ml (12.1–26.5) vs. 53.7 (27.4–73.4), p = 0.007] in diabetics and reduced leukocyte infiltration in carotid lesions of diabetics.ConclusionsHigher NGAL levels in serum and plaques are associated with T2DM in patients with CAS. Metformin significantly reduced the inflammatory burden including NGAL in diabetics. Early treatment of these patients may be recommended, as elevated NGAL levels were linked with vulnerable plaques prone for embolization.

【 授权许可】

CC BY   
© The Author(s) 2017